Sloan-Kettering Institute // Immunology Program

Marcel R. M. van den Brink, MD, PhD

Allogeneic hematopoietic stem cell transplantation (HSCT) is an important therapy for a variety of malignancies, including leukemias, lymphomas, and advanced solid tumors, such as renal cell carcinoma, as well as a number of nonmalignant diseases, such as aplastic anemia and severe combined immunodeficiency. My laboratory uses murine HSCT models to study clinically important problems in HSCT and to test novel therapeutic strategies which can be translated into clinical practice.

The therapeutic benefits of HSCT are not only derived from the opportunity to give higher doses of chemotherapy and/or radiation but also from a so-called graft-versus-tumor (GVT) effect, whereby the graft attacks host malignancy.

HSCT is not without complications: graft-versus-host-disease (GVHD) and immune deficiencies after HSCT are important complications of allogeneic HSCT. GVHD is a progressive systemic illness with immunosuppression, wasting, and specific damage to skin, liver, intestines, and the immune system. Even with prophylaxis, most adults have some degree of GVHD after allogeneic bone marrow transplantation.

HSCT recipients suffer from extensive immune deficiency, which affects the T cell compartment in particular and results in increased susceptibility to infections and malignant relapse.

Our major areas of interest are GVHD, GVT, and immune reconstitution.

Publications

Ghosh A, Dogan Y, Moroz M, Holland AM, Yim N, Rao UK, Young LF, Tannenbaum D, Masih D, Velardi E, Tsai JJ, Jenq RR, Penack O, Hanash AM, Smith M, Piersanti K, Lezcano C, Murphy GF, Liu C, Palomba L, Sauer M, Sadelain M, Ponomarev V, van den Brink MRM. Adoptively transferred TRAIL+ T cells suppress GVHD and augment antitumor activity. Journal of Clinical Investigation. 2013; 123(6):2654–2662. (commentary in J Clin Invest. 2013; Epub ahead of print)

Tsai JJ, Takahashi K, Dudakov JA, Shieh J, Singer NV, West ML, Smith OM, Young LF, Holland AM, Shono Y, Ghosh A, Tran HT, Moore MAS, van den Brink MRM. Nrf2 regulates haematopoietic stem cell function. Nature Cell Biology. 2013; 15(3): 309-16.

Holland AM, Zakrzewski JL, Tsai JJ, Hanash AM, Dudakov JA, Smith OM, West ML, Singer NV, Sun JC, van den Brink MRM. Extrathymic development of murine T cells after bone marrow transplantation. Journal of Clinical Investigation. 2012; 122: 4716-4726. PMCID: PMC3533530;

Hanash AM, Dudakov JA, Hua G, O’Connor MH, Young LF, Singer NV, West ML, Jenq RR, Holland AM, Kappel LW, Ghosh A, Tsai JJ, Rao UK, Yim NL, Smith OM, Velardi E, Liu C, Fouser LA, Kolesnick R, Blazar BR, van den Brink MRM. IL-22 protects intestinal stem cells from immune-mediated tissue damage and regulates sensitivity to graft vs. host disease. Immunity. 2012; 37:339-350. (Previews in Immunity 2012; 37:196). PMCID:PMC3477611;

Dudakov JA, Hanash AM, Jenq RR, Young LF, Singer NV, West ML, Smith OM, Holland AM, Tsai JJ, Boyd RL, van den Brink MRM. IL-22 drives endogenous thymic regeneration in mice. Science. 2012; 336:91-95. (Perspectives in Science 2012; 336:40; Leading Edge Select in Cell 2012; 149:729)